Kinetics of the neutralising antibody response in patients with hand, foot, and mouth disease caused by EV-A71: A longitudinal cohort study in Zhengzhou during 2017-2019.

Qi Qiu,Lu Liang,Peng Li,Peng Cui,Junbo Chen,Lili Wang,Jiaxin Zhou,Kai Wang,Lance Turtle,Yu Li,Yibing Cheng,Hongjie Yu,Yonghong Zhou,Haijun Wang,Yingying Xue

doi:10.1016/j.ebiom.2021.103398

Abstract

BackgroundHand, foot, and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) poses a serious threat to children's health. Kinetics of the neutralising antibody (NAb) response in EV-A71 infected HFMD patients remains unclear. The ideal sampling time of paired serum samples for serological diagnosis of EV-A71 infection is not well defined.MethodsHFMD inpatients admitted to Henan Children's Hospital between February 15, 2017 and February 15, 2018 were enrolled. Serial serum samples collected during hospitalisation and up to 1.5 years after discharge were tested for NAb against EV-A71. Random intercept modelling with B-spline was conducted to characterize the kinetics of the EV-A71 NAb response over time after illness onset.FindingsA total of 524 serum samples from 264 EV-A71 RNA positive HFMD inpatients were collected. NAb titres of EV-A71 infected patients were estimated to increase from 40 (95% CI: 9-180) at the day of onset to the peak of 2417 (95% CI: 1859-3143) at day 13, then remained above 1240 until 26 months. For serological diagnosis of EV-A71 infection, if at least a 4-fold rise in titre was used as the criteria, the acute phase serum should be collected at 0-4 days, the corresponding convalescent serum should be collected 14.9 days (95% CI: 9.1-23.8) after illness onset.InterpretationEV-A71 infection induced a strong and persistent humoral immune response in HFMD patients. The findings provide a scientific support for determining the collection time of paired serum samples for serological diagnosis of EV-A71 infected HFMD patients.FundingNational Science Fund for Distinguished Young Scholars

Highlights

Hand, foot, and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) poses a serious threat to children's health
Few studies have previously described the kinetics of EV-A71 neutralising antibody (NAb) response in HFMD patients, which reported that the antibody response has already initiated on the day of illness onset, and the NAb titre increased with time within a few days
We found that EV-A71 infected HFMD patients hospitalised in Henan children's hospital had a strong and persistent NAb response against EV-A71 during hospitalisation and long time after recovery

Summary

Introduction

Foot, and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) poses a serious threat to children's health. Random intercept modelling with B-spline was conducted to characterize the kinetics of the EV-A71 NAb response over time after illness onset. Findings: A total of 524 serum samples from 264 EV-A71 RNA positive HFMD inpatients were collected. NAb titres of EV-A71 infected patients were estimated to increase from 40 (95% CI: 9-180) at the day of onset to the peak of 2417 (95% CI: 1859-3143) at day 13, remained above 1240 until 26 months. For serological diagnosis of EV-A71 infection, if at least a 4-fold rise in titre was used as the criteria, the acute phase serum should be collected at 0-4 days, the corresponding convalescent serum should be collected 14.9 days (95% CI: 9.1-23.8) after illness onset. The findings provide a scientific support for determining the collection time of paired serum samples for serological diagnosis of EV-A71 infected HFMD patients.

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Conclusion